Alprazolam × Fluvoxamine

Alprazolam is cleared in the liver mainly by CYP3A4, and fluvoxamine inhibits this enzyme (labels of both drugs). The FDA fluvoxamine label describes a study with fluvoxamine 100 mg a day: alprazolam AUC, peak concentration and half-life roughly doubled and its clearance fell by about half. At fluvoxamine 300 mg the effect may be stronger. Both drugs also act on the central nervous system, and the alprazolam SmPC warns that CNS depression can be enhanced when alprazolam is combined with antidepressants.

Drowsiness, slowed reactions, and impaired psychomotor performance and memory, as the FDA fluvoxamine label describes for this combination. In older people, sedation and muscle weakness raise the risk of falls, often with serious consequences (alprazolam SmPC). Driving and operating machinery become riskier. Marked depression of the central nervous system can lead to slowed breathing and coma (alprazolam SmPC).

Avoid the combination where possible: the FDA alprazolam label says so and names fluvoxamine. If it cannot be avoided, start alprazolam at no more than half the usual initial dose and titrate to the lowest effective dose; the fluvoxamine dose does not need changing (FDA fluvoxamine label). The Spanish fluvoxamine SmPC also requires a lower dose of such benzodiazepines during co-treatment, and the alprazolam SmPC requires limiting the dose and duration of alprazolam use with antidepressants. In older people alprazolam is started at a lower dose anyway (alprazolam SmPC). Fluvoxamine is unlikely to change the clearance of benzodiazepines eliminated by glucuronidation, such as lorazepam and oxazepam (FDA fluvoxamine label).